Specific heterocyclic amines are a potent class of foodborne mutagens/carcinogens that are produced by the frying or broiling of meats or fish, heating or meat extracts, and refluxing of appropriate precursor substrates in liquid-reflux model systems. (Sugimura, T. and Sato, S. (1983) Mutagens-carcinogens in foods. Cancer Res., 43, 2415s-2421s; Vuolo, L. L. and Schuessler, G. J. (1985) Review: Putative mutagens and carcinogens in foods. VI. Protein pyrolysate products. Environ. Mutagenesis, 7, 577-598; Prival, J. J. 1984) Carcinogens and mutagens present as natural components of food or induced by cooking. Nutr Cancer, 6, 236-253; Felton, J. S., Knize, M. G., Wood, C., Wuebbles, D. J., Healy, S. K., Stuermer, D. H., Bjeldanes, L. F., Kimble, B. J., and Hatch, F. T. (1984) Isolation and characteristics of new mutagens from fried ground breef. Carcinogenesis, 5, 95-102; Matsushima, T. (1982) Mechanisms of conversion of food components to mutagens and carcinogens. In Arnott, M. S., van Eys, J., Wang, Y.-M. (eds). Molecular Interrelations of Nutrition and Cancer. Raven Press, New York, pp. 507-519; Grivas, S., Nyhammar, T., Olsson, K., and Jagerstad, M. (1985) Formation of a new mutagenic DiMeIQ.sub.x compound in a model system by heating creatinine, alanine and fructose. Mutat. Res., 151, 177-183; Tanaka, T., Barnes, W. S., Weisburger, J. H. and Williams, G. M. (1985) Multipotential carcinogenicity of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in rats. Jpn. J. Cancer Res. (Gann), 76, 570-576; Knudsen, I., ed. (1985) Genetic Toxicology of the Diet. Alan R. Liss, New York). 2-Amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQ.sub.x), and 3,4,8-trimethylimidazo-[4,5-f]quinoxaline (4,8-DiMeIQ.sub.x) are some of the most potent members of this class.
IQ-activated H-ras oncogene has been found in rat hepatocellular carcinoma and sarcoma. (Ishikawa, F., Takalcu, F., Nagao, M., Ochiai, M., Hayashi, K., Takayama, S. and Sugimura, T. (1985) Activated oncogenes in a rat hepatocellular carcinoma induced by 2-amino-3-methylimidazo[4,5-f]quinoline. Jpn. J. Cancer Res. (Gann), 76, 425-428). The IQ-type mutagens, when administered orally, have recently been conclusively demonstrated to be multipotntial carcinogens in rodents, producing neoplasms of the mammary gland, intestine, pancreas, liver, lung, and urinary bladder. (Tanaka, T., Barnes, W. S., Weisburger, J. H. and Williams, G. M. (1985) Multipotential carcinogenicity of the fried food mutagen 2-amino-3-methylimidazo[4,5-f]quinoline in rats. Jpn. J. Cancer Res. (Gann), 76, 570-576; Sugimura, T. (1985) Carcinogenicity of mutagenic heterocyclic amines formed during the cooking process. Mutat. Res., 150, 33-41).
It has been contended that these carcinogens may be the causative agents for major, nutritionally-linked human cancers of the breast, colon, and pancreas, where dietary fat can play a second-stage, promotional role. (Weisburger, J. H. (1977) Current views on mechanisms concerned with the etiology of cancers in the digestive tract. In Farber, E. et al. (eds). Pathophysiology of Carcinogenesis in Digestive Organs. Univ. Tokyo Press, Tokyo, pp. 1-20). These cancers are among the neoplastic diseases having the highest incidence in the United States. (Silverberg, E. (1985) Cancer statistics. Ca-A Cancer J. Clinicians, 35, 5-21). A recent comprehensive review of this subject has just been published by Furihata and Matsushima. Furihata, C. and Matsushima. (Matsushima, T. (1986) Mutagens and carcinogens in foods. Ann Rev. Nutr., 6, 67-94).